Protein Structure

An Introduction
Proteins are polymers of amino acids Vary in size and shape Variations come from
Length Amino acid sequence Number of disulfide bonds Attachment of small molecules or ions

What is a conformation?

An introduction
The function of a protein is determined by its conformation and the chemical properties of its amino acids Functional classes of proteins:
Structural proteins: determine shapes of cells and the ECM Scaffold proteins: bring proteins together into ordered arrays Enzymes Membrane transport proteins Regulatory and signaling proteins Motor proteins

An introduction
How are functions fulfilled:
Binding Catalysis Folding

Proteome?

Protein Structure and Function

Hierarchical Structure of Proteins

An AA sequence folds into a distinct 3D shape that is stabilized by noncovalent interactions between regions in the linear sequence of AA Function is derived from 3D structure 3D structure is determined primarily by noncovalent interaction

Hierarchical Structure of Proteins

Primary Structure of Proteins

Is the linear arrangement of AA Structured by the polymerization of 20 different AA Peptide bonds: covalent amide bond Peptide bonds form through dehydration reaction between an amide group and a carboxyl group Note directionality (C and N terminus)

Peptide Bond Fomration

Secondary Structure
Is a stable spatial arrangement of segments of pp chain held together by H-bonds between backbone Amide and carbonyl groups Principal secondary structures:
- helix - sheet - turn Random coil (no fixed shape)

- helix

- helix
The carbonyl oxygen atom of each peptide bond is h-bonded with the amide h-atom of the aa four residues farther along Hydrophilicity is determined by the characteristics of the side chains Most stable and most common helical form in proteins

- sheet
Consists of laterally packed -strands H-bonding takes place between separate, adjacent -strand Directionality defined by the orientation of the peptide bond

- sheet

- turn
U-shaped secondary structure Composed of four residues Located on the surface of the protein Stabilized by hydrogen bond between end residues Help large proteins to fold into compact structures

- turn

Tertiary Structure
Overall conformation of a polypeptide chain Primarily stabilized by hydrophobic interaction between non-polar side chains, and h-bonds between polar side chains and peptide bonds Not rigidly fixed structure Tertiary structure category:
Fibrous proteins (example?) Globular proteins Intagel membrane proteins

Tertiary Structure

Conformation Depiction of Proteins

Structural Motifs/ Folds

Are particular combinations of secondary and tertiary structures Contribute to the global structure of protein Often performs the same function Examples:
Leucine zipper EF hand: Ca binding basic helix loop helix: DNA binding Zinc finger: DNA/ Rna binding

Structural Motifs/ Folds

Structural and Functional Domains

Distinct regions of a proteins tertiary structure Three main classes of protein domains:
Functional: region that exhibits a particular activity (catalytic/ binding) Structural : a region of about 40 AA, arranged in a stable and distinct secondary or tertiary structure Topological: regions of a protein that are defined by their distinctive spatial relationship to the rest of the protein (cytoplasmic domain of MPs)

Multimeric and macromolecular assemblies

Multimeric also called quaternary structure Monomeric subunits usually disfunctional without assembly Macromolecular assemblies association of different proteins

A Macromolecular Machine